Quantitative Proteomic Analysis of Plasma Exosomes to Identify the Candidate Biomarker of Imatinib Resistance in Chronic Myeloid Leukemia Patients

Autor: Mei-Yong Li, Cui Zhao, Lian Chen, Fang-Yi Yao, Fang-Min Zhong, Ying Chen, Shuai Xu, Jun-Yao Jiang, Yu-Lin Yang, Qing-Hua Min, Jin Lin, Hai-Bin Zhang, Jing Liu, Xiao-Zhong Wang, Bo Huang
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Frontiers in Oncology, Vol 11 (2021)
Druh dokumentu: article
ISSN: 2234-943X
DOI: 10.3389/fonc.2021.779567
Popis: BackgroundImatinib (IM), a tyrosine kinase inhibitor (TKI), has markedly improved the survival and life quality of chronic myeloid leukemia (CML) patients. However, the lack of specific biomarkers for IM resistance remains a serious clinical challenge. Recently, growing evidence has suggested that exosome-harbored proteins were involved in tumor drug resistance and could be novel biomarkers for the diagnosis and drug sensitivity prediction of cancer. Therefore, we aimed to investigate the proteomic profile of plasma exosomes derived from CML patients to identify ideal biomarkers for IM resistance.MethodsWe extracted exosomes from pooled plasma samples of 9 imatinib-resistant CML patients and 9 imatinib-sensitive CML patients by ultracentrifugation. Then, we identified the expression levels of exosomal proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS) based label free quantification. Bioinformatics analyses were used to analyze the proteomic data. Finally, the western blot (WB) and parallel reaction monitoring (PRM) analyses were applied to validate the candidate proteins.ResultsA total of 2812 proteins were identified in plasma exosomes from imatinib-resistant and imatinib-sensitive CML patients, including 279 differentially expressed proteins (DEPs) with restricted criteria (fold change≥1.5 or ≤0.667, p
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